Yuhan Corp. has recently revealed the success of the MARIPOSA clinical trial for Leclaza, its third-generation EGFR tyrosine kinase inhibitor (TKI). This development has sparked interest in whether it will mark the first global introduction of a homegrown anticancer drug.

Professor Cho Byoung-chul, head of the Lung Cancer Center at Yonsei Cancer Center and the principal investigator of MARIPOSA, has sparked more interest by predicting the timeline for Leclaza's entry into the U.S. market.

Holding a news conference at the Korea Pharmaceutical and Bio-Pharma Manufacturers Association (KPBMA) last Friday, Cho introduced the results of the MARIPOSA study presented at the recent European Society for Medical Oncology Annual Meeting (ESMO 2023) and shared his views on the clinical value of the combination of Rybrevant (amivantamab) + Leclaza.

Professor Cho arranged the press conference, unaffiliated with Yuhan and Janssen, the creators of Leclaza and Rybrevant, in order to challenge those who are downplaying the significance of the MARIPOSA trial outcomes.

The MARIPOSA study was selected as the topic of the ESMO 2023 Presidential Symposium, raising expectations of clinical success.

However, the disclosure of progression-free survival (PFS) data from the MARIPOSA study in the abstract before the event led to disappointing responses, as reflected in a sharp drop in Yuhan’s stock price.

For instance, critics noted that the PFS prolongation benefit (7.1 months) of the Rybrevant + Leclaza combination compared to Tagrisso (osimertinib) monotherapy in the MARIPOSA study was shorter than the benefit of Tagrisso in combination with chemotherapy in the FLAURA2 study (8.8 months by investigators and 9.5 months by BICR).

However, Professor Cho quickly pointed out that the two studies were incomparable.

"The MARIPOSA study was designed to perform brain MRIs every eight weeks in all patients, as well as abdominal and chest CTs more frequently than in previous studies, to monitor the changes that the Rybrevant + Leclaza combination was making in patients closely," Cho said. "The MARIPOSA study is the first and only study to do this in a large phase 3 lung cancer trial."

He then dismissed the criticism, stressing that comparing the MARIPOSA study to the FLAURA2 study is like playing on a "tilted field."

In other words, due to frequent imaging, the disease progression itself cannot help but be monitored rapidly, resulting in shorter PFS data compared to other studies, he explained.

Cho presented PFS data adjusted for the assumption that the imaging frequency was the same as the FLAURA2 study design, saying the results showed that the PFS extension benefit (nine months) was similar to that in the FLAURA2 study.

"Whether it is the MARIPOSA study or the FLAURA2 study, overall survival (OS) is more important than PFS in combination therapy studies," he said. "The current OS data maturity must be trending at the same level, and the Rybrevant + Leclaza combination' is showing a strong trend so that we can look forward to the OS data released around next year."

Professor Cho also mentioned the timeline for the U.S. Food and Drug Administration (FDA) filing, which will signal the global launch of Leclaza.

According to Cho, Janssen is expected to file for approval of the Rybrevant + Leclaza combination within the year and Leclaza monotherapy in the first two quarters of next year.

Meanwhile, Janssen recently expressed its official position on the issue, saying, “We will refer to the results of the MARIPOSA study in future regulatory submissions. We cannot comment now on specific license applications or expected timeline."